David Fitch

Using the developmental genetic model system Caenorhabditis elegans, we are characterizing genes responsible for morphogenesis, a collection of fundamental developmental mechanisms that shape and organize cells into particular forms. C. elegans is used for this study because it is complex enough to share components and mechanisms of more complex multicellular animals, but is simple enough to be described in complete terms. The structure we are using as a model for morphogenesis is the sexually dimorphic tail tip. This simple feature is constructed of only 4 cells that, in males only, fuse very late in juvenile ("larval") development and change their cellular structure and position. This results in a blunt shape (the pointy shape of the hermaphrodite tail results from lack of morphogenetic change). We've finished a complete transmission electron microscopic reconstruction of these cellular events using serial sections, providing a descriptive foundation for further functional studies. We have isolated several mutations that fail at certain steps of male tail tip morphogenesis, and are currently cloning the genes defined by these mutations to understand their molecular functions.

Figure: Model of the 4tail tip cells in a C. elegans larva (cuticle removed).

Evolutionary changes in the development of the tail tip have also occurred. Using molecular phylogenetic analysis in combination with a developmental genetic approach, we are reconstructing the developmental changes that have occurred in male tails during the evolution of family Rhabditidae (of which C. elegans is a member). So far we have found several mutations that closely mimic evolutionary changes, suggesting candidate genes that could have been involved in evolutionary changes. These investigations will provide specific information about the genes and processes conserved in morphogenetic mechanisms as well as insight into the ways that these mechanisms can change to produce variation in multicellular form.

Evolution (V23.0058) - Fall term each year
Principles of Evolution (G23.1069) - Spring term every even year
Molecular Evolution Journal Club (G23.3018) - Fall term every year

Participation in the following courses:

• Foundations of Developmental Genetics I and II (G23.2130-31)
• Principles of Biology I (V23.0011)
• Molecular and Cell Biology II (V23.0022)
• Molecular Genetics (G23.2127)
• Advances in Biology (School of Education)

Fulbright Fellowship, Monographic Research on the Systematics of Rhabditidae (Nematoda) and Integrated Student Training in Systematics, January 16, 2000-May 15, 2000; National Science Foundation CAREER Award, IBN-9506844, Genetic and Developmental Mechanisms of a Morphogenetic Program, August 17, 1995-August 16, 2000; Whitehead Fellowship for Junior Faculty in Biomedical or Biological Sciences, Phylogenetic Analysis of Morphogenesis in a Developmental Genetic Model at the Cellular and Ultrastructural Levels, September 1, 1997-August 31, 1999; National Institutes of Health Postdoctoral Fellowship, GM13652, Comparative Genetic Analysis of Nematode Development, February 1, 1990-January 31, 1993.

Date of these PubMed search results: March 24 2020
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1. The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system.
   Elife (2019 Jul 2) PMC6606027 free full-text archive
   Lawson H, Vuong E, Miller RM, Kiontke K, Fitch DH, Portman DS
2. The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28.
   Dev Cell (2019 May 20) PMC6733259 free full-text archive
   Kiontke KC, Herrera RA, Vuong E, Luo J, Schwarz EM, Fitch DHA, Portman DS
3. From "the Worm" to "the Worms" and Back Again: The Evolutionary Developmental Biology of Nematodes.
   Genetics (2018 Oct) PMC6216592 free full-text archive
   Haag ES, Fitch DHA, Delattre M
4. Genome Architecture and Evolution of a Unichromosomal Asexual Nematode.
   Curr Biol (2017 Oct 9) PMC5659720 free full-text archive
   Fradin H, Kiontke K, Zegar C, Gutwein M, Lucas J, Kovtun M, Corcoran DL, Baugh LR, Fitch DHA, Piano F, Gunsalus KC
5. Makorin ortholog LEP-2 regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans.
   Development (2016 Mar 1) PMC4813343 free full-text archive
   Herrera RA, Kiontke K, Fitch DH
6. Comparative validation of the D. melanogaster modENCODE transcriptome annotation.
   Genome Res (2014 Jul) PMC4079975 free full-text archive
   Chen ZX, Sturgill D, Qu J, Jiang H, Park S, Boley N, Suzuki AM, Fletcher AR, Plachetzki DC, FitzGerald PC, Artieri CG, Atallah J, Barmina O, Brown JB, Blankenburg KP, Clough E, Dasgupta A, Gubbala S, Han Y, Jayaseelan JC, Kalra D, Kim YA, Kovar CL, Lee SL, Li M, Malley JD, Malone JH, Mathew T, Mattiuzzo NR, Munidasa M, Muzny DM, Ongeri F, Perales L, Przytycka TM, Pu LL, Robinson G, Thornton RL, Saada N, Scherer SE, Smith HE, Vinson C, Warner CB, Worley KC, Wu YQ, Zou X, Cherbas P, Kellis M, Eisen MB, Piano F, Kionte K, Fitch DH, Sternberg PW, Cutter AD, Duff MO, Hoskins RA, Graveley BR, Gibbs RA, Bickel PJ, Kopp A, Carninci P, Celniker SE, Oliver B, Richards S
7. Nematodes.
   Curr Biol (2013 Oct 7) PMC6827559 free full-text archive
   Kiontke K, Fitch DH
8. A phylogeny and molecular barcodes for Caenorhabditis, with numerous new species from rotting fruits.
   BMC Evol Biol (2011 Nov 21) PMC3277298 free full-text archive
   Kiontke KC, Felix MA, Ailion M, Rockman MV, Braendle C, Penigault JB, Fitch DH
9. Overlap extension PCR: an efficient method for transgene construction.
   Methods Mol Biol (2011) PMID: 22065455
   Nelson MD, Fitch DH
10. Evolution
    In: 2nd, Riddle DL, Blumenthal T, Meyer BJ, Priess JR, editors. Evolution edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1997 Chapter 29 (1997) PMID: 21413220
    Fitch DHA, Kelley Thomas W
11. A bow-tie genetic architecture for morphogenesis suggested by a genome-wide RNAi screen in Caenorhabditis elegans.
    PLoS Genet (2011 Mar) PMC3048373 free full-text archive
    Nelson MD, Zhou E, Kiontke K, Fradin H, Maldonado G, Martin D, Shah K, Fitch DH
12. Phenotypic plasticity: different teeth for different feasts.
    Curr Biol (2010 Sep 14) PMID: 20833313
    Kiontke K, Fitch DH
13. Evolution of early embryogenesis in rhabditid nematodes.
    Dev Biol (2009 Nov 1) PMC2763944 free full-text archive
    Brauchle M, Kiontke K, MacMenamin P, Fitch DH, Piano F
14. Dropout alignment allows homology recognition and evolutionary analysis of rDNA intergenic spacers.
    J Mol Evol (2008 Apr) PMID: 18363028
    Ryu S, Do Y, Fitch DH, Kim W, Mishra B
15. Introduction to nematode evolution and ecology.
    WormBook (2005 Aug 31) PMC4781023 free full-text archive
    Fitch DH
16. The phylogenetic relationships of Caenorhabditis and other rhabditids.
    WormBook (2005 Aug 11) PMC4781183 free full-text archive
    Kiontke K, Fitch DH
17. Trends, stasis, and drift in the evolution of nematode vulva development.
    Curr Biol (2007 Nov 20) PMID: 18024125
    Kiontke K, Barriere A, Kolotuev I, Podbilewicz B, Sommer R, Fitch DH, Felix MA
18. Caenorhabditis evolution: if they all look alike, you aren't looking hard enough.
    Trends Genet (2007 Mar) PMID: 17275130
    Haag ES, Chamberlin H, Coghlan A, Fitch DH, Peters AD, Schulenburg H
19. Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin-41 in C. elegans male tail tip morphogenesis.
    Dev Biol (2006 Sep 1) PMID: 16806150
    Del Rio‑Albrechtsen T, Kiontke K, Chiou SY, Fitch DH
20. Evolution: an ecological context for C. elegans.
    Curr Biol (2005 Sep 6) PMID: 16139194
    Fitch DH
21. Autosomal genes of autosomal/X-linked duplicated gene pairs and germ-line proliferation in Caenorhabditis elegans.
    Genetics (2005 Apr) PMC1449572 free full-text archive
    Maciejowski J, Ahn JH, Cipriani PG, Killian DJ, Chaudhary AL, Lee JI, Voutev R, Johnsen RC, Baillie DL, Gunsalus KC, Fitch DH, Hubbard EJ
22. Initial Sequence and Protein Modeling Results of a Mitochondrial Genome Project on Understudied Invertebrate Phyla.
    Biol Bull (2004 Oct) PMID: 27690613
    Robbins GE, Giribet G, Kiontke K, Fitch DH, Boore JL, Campbell RK
23. Caenorhabditis phylogeny predicts convergence of hermaphroditism and extensive intron loss.
    Proc Natl Acad Sci U S A (2004 Jun 15) PMC428462 free full-text archive
    Kiontke K, Gavin NP, Raynes Y, Roehrig C, Piano F, Fitch DH
24. The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics.
    PLoS Biol (2003 Nov) PMC261899 free full-text archive
    Stein LD, Bao Z, Blasiar D, Blumenthal T, Brent MR, Chen N, Chinwalla A, Clarke L, Clee C, Coghlan A, Coulson A, D'Eustachio P, Fitch DH, Fulton LA, Fulton RE, Griffiths‑Jones S, Harris TW, Hillier LW, Kamath R, Kuwabara PE, Mardis ER, Marra MA, Miner TL, Minx P, Mullikin JC, Plumb RW, Rogers J, Schein JE, Sohrmann M, Spieth J, Stajich JE, Wei C, Willey D, Wilson RK, Durbin R, Waterston RH
25. Absence of wolbachia in nonfilariid nematodes.
    J Nematol (2003 Sep) PMC2620650 free full-text archive
    Bordenstein SR, Fitch DH, Werren JH
26. One small step for worms, one giant leap for "Bauplan"?
    Evol Dev (2002 Jul-Aug) PMID: 12168615
    Fitch DH, Sudhaus W
27. TLP-1 is an asymmetric cell fate determinant that responds to Wnt signals and controls male tail tip morphogenesis in C. elegans.
    Development (2002 Mar) PMID: 11880358
    Zhao X, Yang Y, Fitch DH, Herman MA
28. Evolution of "rhabditidae" and the male tail.
    J Nematol (2000 Sep) PMC2620451 free full-text archive
    Fitch DH
29. Morphogenesis of the Caenorhabditis elegans male tail tip.
    Dev Biol (1999 Mar 1) PMID: 10049567
    Nguyen CQ, Hall DH, Yang Y, Fitch DH
30. Evolution of male tail development in rhabditid nematodes related to Caenorhabditis elegans.
    Syst Biol (1997 Mar) PMID: 11975351
    Fitch DH
31. Variable cell positions and cell contacts underlie morphological evolution of the rays in the male tails of nematodes related to Caenorhabditis elegans.
    Dev Biol (1995 Aug) PMID: 7649384
    Fitch DH, Emmons SW
32. 18S ribosomal RNA gene phylogeny for some Rhabditidae related to Caenorhabditis.
    Mol Biol Evol (1995 Mar) PMID: 7700158
    Fitch DH, Bugaj‑Gaweda B, Emmons SW
33. Widespread occurrence of the Tc1 transposon family: Tc1-like transposons from teleost fish.
    Mol Gen Genet (1994 Sep 28) PMID: 7969029
    Radice AD, Bugaj B, Fitch DH, Emmons SW
34. Low codon bias and high rates of synonymous substitution in Drosophila hydei and D. melanogaster histone genes.
    Mol Biol Evol (1993 Mar) PMID: 8487638
    Fitch DH, Strausbaugh LD
35. Fetal recruitment of anthropoid gamma-globin genes. Findings from phylogenetic analyses involving the 5'-flanking sequences of the psi gamma 1 globin gene of spider monkey Ateles geoffroyi.
    J Mol Biol (1992 Apr 5) PMID: 1569563
    Hayasaka K, Fitch DH, Slightom JL, Goodman M
36. Pattern formation in the nematode epidermis: determination of the arrangement of peripheral sense organs in the C. elegans male tail.
    Development (1991 Oct) PMID: 1782863
    Baird SE, Fitch DH, Kassem IA, Emmons SW
37. Duplication of the gamma-globin gene mediated by L1 long interspersed repetitive elements in an early ancestor of simian primates.
    Proc Natl Acad Sci U S A (1991 Aug 15) PMC52302 free full-text archive
    Fitch DH, Bailey WJ, Tagle DA, Goodman M, Sieu L, Slightom JL
38. Phylogenetic scanning: a computer-assisted algorithm for mapping gene conversions and other recombinational events.
    Comput Appl Biosci (1991 Apr) PMID: 2059846
    Fitch DH, Goodman M
39. Molecular evolution of the psi eta-globin gene locus: gibbon phylogeny and the hominoid slowdown.
    Mol Biol Evol (1991 Mar) PMID: 2046542
    Bailey WJ, Fitch DH, Tagle DA, Czelusniak J, Slightom JL, Goodman M
40. On the origins of tandemly repeated genes: does histone gene copy number in Drosophila reflect chromosomal location?
    Chromosoma (1990 Apr) PMID: 2113451
    Fitch DH, Strausbaugh LD, Barrett V
41. Primate evolution at the DNA level and a classification of hominoids.
    J Mol Evol (1990 Mar) PMID: 2109087
    Goodman M, Tagle DA, Fitch DH, Bailey W, Czelusniak J, Koop BF, Benson P, Slightom JL
42. Molecular history of gene conversions in the primate fetal gamma-globin genes. Nucleotide sequences from the common gibbon, Hylobates lar.
    J Biol Chem (1990 Jan 15) PMID: 2295619
    Fitch DH, Mainone C, Goodman M, Slightom JL
43. Molecular phylogeny of the family of apes and humans.
    Genome (1989) PMID: 2687100
    Goodman M, Koop BF, Czelusniak J, Fitch DH, Tagle DA, Slightom JL
44. The spider monkey psi eta-globin gene and surrounding sequences: recent or ancient insertions of LINEs and SINEs?
    Genomics (1988 Oct) PMID: 2852163
    Fitch DH, Mainone C, Slightom JL, Goodman M